Classically, use of helium as a substitute for nitrogen in the breathing gas during deep sea diving is well known. The helium prevents nitrogen from dissolving in body fluids at high concentration under pressure. This results in the painful condition known as “the bends”, which is one of the first known examples of medical therapy using a gaseous agent.
Oxygen and other anesthetic gases and liquids are now routinely used for therapeutic purposes. Generally, gases are inhaled directly into the body directly. More recently, with the advent of open-heart surgery, oxygen has been administered to the body via extracorporeal blood oxygenators. Further, in the last decade, another gas, nitric oxide, was found to have potent vessel dilatory activity.
Most gases that could be considered for therapeutic applications are hydrophobic low molecular weight compounds of low water solubility. These gases are considered to have the ability to rapidly move through tissue by virtue of their high diffusivity and to cross the lipid membranes of target cells by virtue of their hydrophobic character. This is in contrast to movement of other bioactive agents such as ions, peptides and hormones, whose entry into cells requires specific interactions with cell surface receptors and/or similar transport mechanisms such as ion channeling, endocytosis or pinocytosis.
The mobility of most gaseous agents is between that of the extremely small and rapid acting electron delivered for cardiac pacing or neuro-stimulation therapies and that of slower acting, higher molecular weight agents such as hormones, peptides and molecular biological vectors. The primary delivery route used in gaseous therapy has been through use of extracorporeal devices for inhalation into the lung or to exchange gases in the blood, such as with a blood oxygenator.
The traditional and most widely used means for delivering a gas to the body is by inhalation. Nitrous oxide, xenon, or vapors of highly volatile liquids such as isoflurane are inhaled to produce systemic analgesia or anesthesia. The oxygen concentration of the inhaled gas stream may also be adjusted during anesthesia or during other medical procedures to improve blood oxygenation. Nitric oxide can also be beneficially administered via inhalation to improve lung ventilation by virtue of its vasodilating effect within the alveoli. The physiological effects of inhaled nitric oxide, with a half-life of seconds or less in the body, are limited to the lung while anesthetic gases produce more systemic effects because of their longer half-lives.
As seen from the previous description, the art describes various modalities of producing gaseous agents for delivery though an extracorporeal devices. The present invention provides an important advancement in the art by providing an internal implantable device for generating gaseous agents and their use in therapy. More specifically, the present invention provides a fully implantable medical device system for controlled delivery of a gaseous agent for therapeutic use. Optionally these devices can be integrated with other implantable medical devices. Having a local implantable source of gaseous agent provides a means for better controlled local delivery to the targeted tissue and use of lower concentrations of the gaseous agent.